| Project/Area Number |
16390540
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pathobiological dentistry/Dental radiology
|
|---|
| Research Institution | The University of Tokushima (2005)
Kagoshima University (2004) |
|---|
Principal Investigator |
ITO Hiro-O The University of Tokushima, Institute of Health Bioscience, Professor, 大学院・ヘルスバイオサイエンス研究部, 教授 (40213079)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SOUTOME Sakiko Kagoshima University, Hospital, Research Associate, 医学部・歯学部附属病院, 助手 (20325799)
軒原 清史 (株)ハイペップ研究所, 最高科学責任者・CEO (60137073)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2005: ¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 2004: ¥7,300,000 (Direct Cost: ¥7,300,000)
|
|---|
| Keywords | Peptide Libraries / Decombolution / Oral Bacteria / Infective Endocarditis / Positional Scanning / Monoclonal Antibodies / Fibronectin / Natural Product Libraries / デコンボルーション |
|---|
| Research Abstract |
Infective endocarditis is often caused by passage of oral endogenous bacteria into the blood stream. Such bacteremia occurs after tooth extraction, and occasionally even after brushing of the teeth. Abnormal or damaged heart valves, including artificial valves, show high risk of infection. Antibiotics are widely used to prevent this infection, however, frequent use of these have resulted in the generation of resistant mutants, which generate serious social problems. Thus, the development of more effective and safer drugs for the prevention of such infections is very desirable. The adhesion of bacteria to fibronectin, one of the major extracellular matrix protein exposed on the wound endocardia, is considered critical for the infection. We have previously found a novel mode of interaction between endocarditis-causing bacteria and human fibronectin. The present study focuses on the discovery of candidate compounds that inhibit the association between microorganisms and fibronectin. Positional scanning libraries (PSL) with N-terminal biotinylated 6-mer peptides have been constructed and screened for binding to a monoclonal antibody for fibronectin that inhibits the bacterial fibronectin-binding. The consensus sequences derived from these experiments are expected to be structural mimetics of the local structure of fibronectin involved in the bacterial adhesion. Since individual synthetic 6-mer peptides did not show the desired action, discontinuous epitopes can be envisaged and therefore a 9-mer-PSL was constructed to reveal conformational epitopes. In the second Library, several 9-mer peptides based on the screening were synthesized and gave improved results.
|
